The combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that ...forms a six-membered ring is formally either a 5 + 1-, 4 + 2-, 2 + 2 + 2-, or 3 + 3-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted 4 + 2-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise 3 + 3-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention. In this Account, we present the development of stepwise 3 + 3-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of 3 + 3-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal 3 + 3-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for 3 + 3-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for 3 + 3-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative 3 + 2-cycloaddition across the carbon–carbon double bond of the vinylcarbene. Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of stable dipoles, to form 3 + 3-cycloaddition products having the β-ketoester functionality (in dihydrooxazines, tetrahydropyridazines, pyrazolidinone and pyraxole derivatives, dihydroquinolines, and quinolizidines, for example) in high yield. Two ways to access these metallo-enolcarbenes, either by dinitrogen extrusion from enoldiazoacetate esters or by rearrangement of donor–acceptor cyclopropenes, enhance the versatility of the process. The 3 + 3-cycloaddition methodology is a complementary strategy to 4 + 2-cycloaddition for the synthesis of heterocyclic compounds having six-membered rings. High levels of enantioselectivity are obtained with the use of chiral ligands on transition metal catalysts that include those on dirhodium(II) and silver(I).
Toss the olefin into the porphyrin: The development of chiral cobalt(II)–porphyrin catalysts by straightforward coupling processes has made possible the additions of diazocarbonyl compounds to a ...broad spectrum of olefins to access functionalized cylopropanes. The cyclopropanation reactions demonstrate high product yields, exceptional diastereoselectivity, and excellent enantiocontrol.
Catalytic Carbene Insertion into C−H Bonds Doyle, Michael P; Duffy, Richard; Ratnikov, Maxim ...
Chemical reviews,
2010-Feb-10, Letnik:
110, Številka:
2
Journal Article
Recenzirano
The catalytic insertion of carbene into carbon-hydrogen bonds is examined. Although few of these reactions have produced the desired result, the potential for forming carbon-carbon bonds keeps ...researchers interested.
A highly enantioselective preparation of substituted pyrrolidines and 1,2-oxazinanes has been achieved via stereoretentive 3 + 2/3 + 3-cycloaddition of nonracemic donor–acceptor cyclopropanes with ...imines, triazines, and nitrones in good to high yields with broad scope under mild reaction conditions. In comparison with the well-documented approach to donor–acceptor cyclopropane reactions using racemic cyclopropane reactants and a catalyst with chiral ligands, this report features applications of enantioenriched donor–acceptor cyclopropanes as cycloadduct reactants with achiral catalysts.
A chiral copper(I) complex catalyzes reactions of symmetric diaziridines with enol diazo compounds, which react through N−N bond ring opening in a formal 3+3 cycloaddition to form four chiral centers ...with high stereocontrol. A broad spectrum of bridged dinitrogen heterocycles were obtained in high yields and excellent diastereo‐ and enantioselectivities from γ‐substituted enol diazoacetates, while their geometrical isomers gave different enantioselectivities. Donor–acceptor cyclopropenes formed from the geometrical isomers of the γ‐substituted enol diazoacetates underwent catalytic ring opening to give only the Z isomer of the metalloenolcarbene intermediate, provided excellent yields and selectivities for the 1,5‐diazabicyclon.3.1non‐2‐ene derivatives.
Symmetric diaziridines underwent N−N bond ring opening in a formal 3+3 desymmetrization cycloaddition with enol diazo compounds. A chiral copper(I) complex catalyzes the enantioselective variant of this process. The use of donor–acceptor‐substituted cyclopropenes as the metalloenolcarbene precursors in the presence of the same chiral CuI/bisoxazoline complex delivered various chiral 1,5‐diazabicyclon.3.1non‐2‐enes with better enantioselectivity.
Iron(III) chloride catalyzes the aerobic oxidation of tertiary anilines, including tetrahydroisoquinolines, to form reactive iminium ion intermediates that undergo Mannich reactions with ...silyloxyfurans, nitroalkanes, and other nucleophiles to give the corresponding butenolides, nitro compounds, and α-substituted tetrahydroisoquinolines, respectively, in good to excellent yields.
Dirhodium compounds are emerging as highly efficient catalysts for diverse reactions, and those with carboxamidate ligands have the broadest applications. The unique features of these compounds are ...their structural rigidity, ease of ligand exchange, open diaxial sites for coordination with Lewis bases, and their low oxidation potential. As consequences of this, dirhodium carboxamidates are efficient and effective catalysts for metal carbene reactions, Lewis acid-catalyzed processes, and chemical oxidations. With chiral carboxamidate ligands these dirhodium compounds show exceptional enantiocontrol for intramolecular cyclopropanation and carbon−hydrogen insertion reactions of diazoacetates, and they are also highly efficient and selective for hetero-Diels−Alder reactions. Their limitations lie in their moderate reactivities for metal carbene generation and Lewis acid catalysis and in the cost of the precious metal rhodium.
The combination of levulinic acid and sodium dodecyl sulfate (SDS) in recent years has shown considerable promise as an antimicrobial intervention. Both ingredients have been designated by the U.S. ...Food and Drug Administration (FDA) as Generally Recognized as Safe (GRAS) for being used as a flavoring agent and multipurpose food additive, respectively. The use of levulinic acid and SDS alone has limited antimicrobial efficacy on tested microorganisms, and synergism between levulinic acid and SDS has been observed. The postulated mechanism of action of the synergistic effect is presented. The antimicrobial efficacy of levulinic acid plus SDS remains high even when organic materials are present. The other features, including penetration, foamability, and being readily soluble, extend its potential applications to disinfection of difficult-to-access areas and control of foodborne pathogens both in a planktonic state and in a biofilm. These features indicate that the levulinic acid plus SDS combination may have the potential to be applied within the food processing environment on a large scale.
![The [3 + 3]-Cycloaddition A...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0001-4842_1520-4898/small "The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts")
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